Various models of chromosome structure and function have implicated special classes of nucleotide sequences, especially repeated sequences, as packing principals in chromosome folding, as initiation sites for replication and recombination, and as controlling elements in gene expression and the further processing of transcriptional products. A critical evaluation of such models requires an understanding of the topological relationships between different types of sequences. We are engaged in the analysis of sequence organization in the Drosophila genome by denaturation mapping. Computer aided formal procedures have been developed which allow classification of individual nuclear DNA fragments or of batches of fragments with respect to the presence or absence of ordered structures. Also alternative ways to generate novel denaturation patterns are being explored. Interspecies comparisons of denaturation maps of Drosophila mitochondrial DNAs have suggested extensive sequence homologies, which are now being measured by heteroduplex analysis using both electron microscopy and biochemical hybridization techniques. BIBLIOGRAPHIC REFERENCES: Bultmann, H., Zakour, R.A., and M.A. Sosland: Evolution of Drosophila mitochondrial DNAs: Comparison of denaturation maps. Biochim. Biophys. Acta 454, 21-44, (1976). Zakour, R.A., and H. Bultmann: Drosophila melanogaster: Drosophila virilis heteroduplex mitochondrial DNAs. Genetics 83, 586 (1976).